We have developed and applied methodology for measuring regional and total body release and neuronal uptake of norepinephrine (NE), the sympathetic neurotransmitter, and have assessed the effects of various stimuli (isoproterenol, clonidine, manipulations of dietary salt) on sympathetic activity. Total body spillover of NE into the circulation is increased by playing an electronic game, which also increases blood pressure, pulse rate, cardiac output, and forearm blood flow. Applying these methods to patients with essential hypertension should allow testing of the long-standing hypothesis that excessive sympathetic responses to mental challenge characterizes young patients with hypertension or subjects at risk for developing established hypertension. The clonidine suppression test can be conducted without controlling dietary salt intake and can be used to define the neurogenic contribution to hypertension. Isoproterenol stimulates NE release without affecting plasma epinephrine (E) and may therefore be helpful in studying pre-synaptic beta-adrenoceptor function in hypertensive patients. Circulating beta-adrenoceptor agonists do not increase adrenocorticotropin (ACTH).